Stabilization of solutions of 3-isothiazolones employing certain metal nitrates and nitrites

ABSTRACT

Solution of 3-isothiazolones are stabilized against chemical decomposition of the isothiazolone by adding thereto a metal nitrate or a metal nitrite.

Unite States Patent Miller et al.

STABILIZATION OF SOLUTIONS OF 3-ISOTHIAZOLONES EMPLOYING CERTAIN METALNITRATES AND NITRITES Inventors: George A. Miller, Glenside; Ernest ID.Weiler, Ambler, both of Pa.

Rohm and Haas Company, Philadelphia, Pa.

Filed: Feb. 28, 1973 Appl. No; 336,659

Assignee:

US. Cl 424/270, 252/397, 260/302 A,

260/304, 424/245 Int. Cl ..A01n 9/12 Field of Search 424/270; 252/397;

[ Mar. 11, 1975 References Cited OTHER PUBLICATIONS Chemical Abstracts,Vol. 72 (1970), p. ll1459n. Chemical Abstracts, Vol. 51 (1957), p.13306f. Chemical Abstracts. Vol. 64 (1966) p. 6145c.

Plilillll') E.\-aminerVincent D. Turner Attorney, Agent, or FirmWilliamE. Lambert, lll; Betty A. Narducci [57] ABSTRACT Solution of3-isothiazolones are stabilized against chemical decomposition of theisothiazolone by adding thereto a metal nitrate or a metal nitrite.

8 Claims, N0 Drawings 1 STABILIZATION OF SOLUTIONS OF 3-ISOTI-IIAZOLONESEMPLOYIN G CERTAIN METAL NITRATES AND NITRITES This invention relates toa method of stabilizing solutions of 3-isothiazolones and to solutionsstabilized thereby.

Many 3-isothiazolones, especially those disclosed in US. Pat.application Ser. No. 836,660, filed on June 25, 1969, by Sheldon N.Lewis, et al., now US. Pat. No. 3,761,488, granted Sept. 25, 1973. Ser.No. 855,046, filed on Sept. 3, 1969, by Sheldon N. Lewis et al., andSer. No. 142,775, filed on May 12, 1971, by George A. Miller et al., US.Pat. No. 3,517,022, of George A. Miller et al., granted June 23, 1970,and US. Pat. No. 3,544,580, of Sheldon N. Lewis et al., granted Dec. 1,1970, have been found to possess excellent biocidal properties and to beextremely useful as broad spectrum microbicides. In various types ofapplications, it is frequently necessary or convenient to formulate the3-isothiazolones in solution, especially using water or polar organicsolvents, such as alcohols, as solvents. While such formulation has noeffect on the stability or function of the 3-isothiazolones if usedrelatively quickly, extended storage of the formulated solutions,especially at elevated temperatures, may result in chemicaldecomposition of the 3-isothiazolone active ingredient and, thus, leadto reduced biocidal effectiveness of the solution.

lt has now been found that a solution of a 3- isothiazolone or of amixture of 3-isothiazolones can be stabilized against chemicaldecomposition of the isothiazolone by the addition to the solution ofametal nitrate or a metal nitrite. In a preferred embodiment of theinvention, the 3-isothiazolone will be either a compound of the formulawherein Y is a hydrogen atom, an alkyl group of 1 to 18 carbon atoms,alkenyl or alkynyl group of2 to 18 carbon atoms, and preferably 2 to 4carbon atoms, a cycloalkyl group of 3 to 12 carbon atoms, preferablyhaving a 3 to 8 carbon atom ring, an aralkyl group of up to 10 carbonatoms, or an aryl group of up to 10 carbon atoms; 5

R is a hydrogen atom, a halogen atom, or an alkyl group, preferablyhaving 1 to 4 carbon atoms;

R is a hydrogen atom, a halogen atom, or an alkyl group, preferablyhaving 1 to 4 carbon atoms; or R and R can be taken together to completea benzene ring, optionally substituted with one or more halogen atoms,nitro groups, (C C )alkyl groups, cyano groups, (C,-C,)alkoxy groups, orthe like; or

a melt salt complex of the formula wherein Y, R, and R are as definedabove,

M is a cation of a metal, such as barium, cadmium,

calcium, chromium, cobalt, copper, iron, lead, lithium, magnesium,manganese, mercury, nickel, sodium, silver, strontium, tin, zinc, or thelike;

X is an anion forming a compound with the cation M, wherein the compoundhas sufficient solubility to form a metal salt complex;

a is the integer l or 2; and

n is an integer which for the anion X satisfies the valence of thecation M.

As used in the specification and claims, the term alkyl group isintended to include unsubstituted alkyl groups as well as substitutedalkyl groups in which one or more of the hydrogen atoms are replaced byanother substituent group. Examples of the substituted alkyl groupswhich characterize the 3-isothiazolones and the metal salts complexes ofthe invention include hydroxyalkyl, haloalkyl, cyanoalkyl,alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, carboxyalkyl,carbalkoxyalkyl, alkoxyalkyl, aryloxyalkyl, alkylthioalkyl,arylthioalkyl, isothiazolonylalkyl, haloalkoxyalkyl, carbamoxyalkyl,azacycloalkylalkyl, such as morpholinoalkyl, piperidinoalkyl, andpyrrolidonylalkyl, and the like. The terms alkenyl group and alkynylgroup are intended to include unsubstituted alkenyl and alkynyl groupsas well as substituted groups such as haloalkenyl, haloalkynyl, and thelike.

The term aralkyl groups is intended to include unsubstituted aralkylgroups as well as substituted aralkyl groups having one or more of thehydrogen atoms on either the aryl ring or the alkyl chain replaced byanother substituent group. Examples of the substituted aralkyl groupswhich characterize the 3-isothiazolones and the metal salt complexes ofthe invention include halogen-, nitro, (C -C )alkyl-, or (C -C)alkoxysubstituted aralkyl groups, and the like.

The term aryl group is intended to include unsubstituted aryl groups,such as phenyl, naphthyl, or pyridyl, as well as such aryl groups havingone or more of the hydrogen atoms on the aryl ring replaced by anothersubstituent group. Examples of such substituent groups include halogen,cyano, nitro, (C -C )alkyl, (C C )alkoxy, (C -C )alkylacylamino, (C -C)carba1koxy, sulfamyl, and the like.

Representative Y substituents include hydrogen, methyl, ethyl, propyl,isopropyl, butyl, hexyl, octyl, decyl, pentadecyl, octadecyl,cyclopropyl, cyclohexyl, benzyl, 3,4-dichlorobenzyl, 4-methoxybenzyl, 4-chlorobenzyl, 3,4-dichloropenyl, 4-methoxyphenyl, hydroxymethyl,chloromethyl, chloropropyl, diethylaminoethyl, cyanoethyl,carbomethoxyethyl, ethoxyethyl, 2-methoxy-1-bromoethyl,3,3,S-trimethylcyclohexyl, phenoxyethyl, p-chloroanilinomethyl,phenylcarbamoxymethyl, hydroxybutyl allyl, propynyl, vinyl.carboxyethyl, l-isothiazolonylethyl, 1,2,2-trichlorovinyl, and the like.Representative R and R substituents include hydrogen, bromine, chlorine,iodine, methyl. ethyl, propyl, isopropyl, butyl, t-butyl, and the like.The alkyl substituents represented by Y, R, and R can have eitherbranchedor straight-chain spatial configuration.

Among the anions which X can represent are chloride, bromide, iodide,sulfate, nitrate, nitrite, acetate, chlorate, perchlorate, bisulfate,bicarbonate, oxalate,

maleate, p-toluenesulfonate, carbonate, phosphate, and the like. Thepreferred metals from which M is derived are calcium, copper, magnesium,manganese, nickel, and zinc. Among the metal cations embraced by M arecationic complexes sof the metal ions, including complexes with ammonia,simple organic amines, and various heterocyclic organic amines such aspyridines, pyrimidines, and the like.

A wide variety of metal nitrates and metal nitrites can be used tostabilize solutions of isothiazolones and generally any metal nitrate ornitrite which has appreciable solubility in the solution will exert astabilizing effect. Among the useful metal nitrates are sodium nitrate,potassium nitrate, calcium nitrate, magnesium nitrate, copper nitrate,ferric nitrate, ferrous nitrate, nickel nitrate, zinc nitrate, bariumnitrate, manganese nitrate, silver nitrate, cobalt nitrate, and thelike. Among the useful metal nitrites are sodium nitrite, potassiumnitrite, calcium nitrite, magnesium nitrite, and the like. In apreferred embodiment of the invention, a metal nitrate is used tostabilize the isothiazolone solution. Surprisingly, other common metalsalts, including carbonates, sulfates, chlorates, perchlorates, andchlorides are ineffective in stabilizing isothiazolones solutions.

Generally, the metal nitrate or nitrite is used to stabilize theisothiazolone solution in an amount of about 1 percent to about 30percent, preferably about percent to about percent, by weight based onthe weight of the solution. For example, in a 25 percent by weightsolution of an isothiazolone, about 10 percent to about percent byweight of the metal nitrate or nitrite will generally be sufficient tostabilize the solution against chemical decomposition. Of course, theamount of metal nitrate or nitrite needed to stabilize the solution willbe partly dependent on the solvent, the isothiazolone and itsconcentration, the nitrate or nitrite used, the length of time thesolution is to be kept, and other related factors.

In a preferred embodiment of the invention, the metal nitrates and metalnitrites are used to stabilize solutions of 3-isothiazolones in waterand in polar organic solvents, including alcohols such as methanol,ethanol, propanol, butanol, ethylene glycol, propylene glycol,dipropylene glycol, polypropylene glycol, polyethylene glycol, methylcellosolve, and the like. Among the applications in which solutions ofisothiazolones are used are as watercooling system microbicides, aspreservatives for aqueous dispersions of organic polymers, as wood pulpwhite water slimicides, as cosmetic preservatives, as cutting oil, jetfuel, and heating oil preservatives, and the like. Solutions ofisothiazolones are also often used applying an isothiazolone to a solidsubstrate, such as fabric, leather, or wood, as a preservative,especially in automated treating processes.

The preparation and properties of representative 3- isothiazolones whichin solution are stabilized by the metal nitrates and nitrites aredescribed in U.S. Pat. applications Ser. No. 836,660, filed June 25,1969, by Sheldon N. Lewis et 211., now U.S. Pat. No. 3,761,488, grantedSept. 25, 1973. Ser. No. 855,046, filed on Sept. 3, 1969, by Sheldon N.Lewis et al., and Ser. No. 142,775, filed on May 12, 1971, by George A.Miller et al., and in U.S. Pat. Nos. 3,517,022 of George A. Miller eta1., granted June 23, 1970 and 3,544,480, of Sheldon N. Lewis et al.,granted Dec. 1, 1970. When solutions of metal salt complexes of theisothiazolones arte to be used, it may be advantageous to prepare thecomplexes in situ by neutralization of a salt, such as the hydrochloridesalt, of the appropriate isothiazolone with a basic metal compound, suchas an oxide or carbonate. Optionally, up to about one half moleequivalent of a metal nitrate is added to these solutions, prior to theaddition of the metal nitrate stabilizer.

The following examples will further illustrate this invention, but arenot intended to limit it in any way. All parts and percentages are byweight and all temperatures in Centigrade, unless otherwise stated.Percentages of the metal nitrates and metal nitrites are based on themolecular weight of the common commercial form.

EXAMPLE 1 This example shows the effect of various metal nitrates instabilizing aqueous solutions of 3- isothiazolone metal salt complexes.The metal salt complex used in making the aqueous solutions of thisrepresentative example is a 3:1 weight ratio of the calcium chloridecomplexes of 5-chloro-2-methyl-3- isothiazolone and2-methyl-3-isothiazolone. Aqueous solutions containing 25 percent byweight of the metal salt complex and from 1.4 to 28.7 percent by weightof the metal nitrate based on the molecular weight of the commoncommercial form are prepared and stored for up to 84 days at 50C. Fromtime to time the solutions are visually examined, and rated as passed"if they remain clear and contain no or minor traces of yellowprecipitate. When the solution become brown in color or containsignificant amounts of brown or black precipitates they are ratedfailed. Table I summarizes the results of these tests.

TABLE X NON-AQUEOUS SOLUTlONS OF S-CHLOROQ-METHYU3-lSOTHlAZOLONE/2-METHYL-3JSOTHlAZOLONE (93:7) (25% by weight, 50C) This example showsthe ineffectiveness of metal salts other than metal nitrates andnitrites in stabilizing aqueous solutions of 3-isothiazolone metal saltcomplexes.

Following the procedure of Example 1 other metal salts were added toaqueous solutions of the same metal salt complex, and rated in a similarway. Table [1 summarizes the results of these tests.

TABLE II AQUEOUS SOLUTIONS OF 3-lSOTHlAZOLONE METAL SALT COMPLEX (25% byweight, 50C) Appearance (days) Metal Salt Weight Failed Passed none 10CaCO l 7 CuCl .2H O 12.7 10 CuSO.,.5H O 15.9 10 Fexson su o 14,1 10

5 TABLE II-Continued AQUEOUS SOLUTIONS OF B-ISOTHIAZOLONE METAL SALTCOMPLEX (25% by weight. 50C) Appearance (days) This example showsquantitatively the extent to which chemical decomposition of3-isothiazolone' metal salt complexes in solution is inhibited by metalnitrates and metal nitrites. I

Solutions of the metal salt complex used in Example I (25 percent byweight) stabilized with various metal The abovedata demonstratestheeffectiveness of metal nitrates and metal nitrites in inhibitingchemical decomposition of aqueous solutions of 3-isothiaz0lone metalsalt complexes.

EXAMPLE 4 This example shows the effect of various metal nitrates instabilizing aqueous solutions of 3- isothiazolone metalsaltcomplexesprepared in situ.

Solutions (25 percent by weight) ofa 3:1 weight ratio of thehydrochloride salts of 5-chloro-2-methyl-3- isothiazolone and2-methyl-3-isothiazolone are neutralized with 0.5 or 1.0 mole-equivalentof a metal oxide or metal carbonate. To the solutions is then added 0.5mole-equivalent of a metal nitrate and up to 25 percent by weight ofadditional metal nitrate as a stabilizer. The

. solutions are stored at 50C for the time indicated and evaluated byglc to determine the amount of decomposition of the isothiazolone. TableIV summarizes the results of these tests.

TABLE IV DECOMPOSITION OF METAL SALT COMPLEXES PREPARED IN SITU ComplexFormed Metal by weight, 50C) Stabilizer Base Mole-equiv. Nitrate MetalNitrate; wt. Time Decomposition CaO CaCh; l.0 none none 10 days 100 CaOI caCl 0.5 Ca(NO Ca(NO .4H O; 25% 6 months 5 CaCO CaCI 0.5 Zn(NO Zn(NO),.6H O; 25% 6 months 5 CaCO CaCl 0.5 Mn(NO Mn(NO 25% 6 months l MgOMgCl 0.5 Mg(NO Mg(NO .6H O; 25% 3 months i 0 6 months l0 MgCO MgCl,; 0.5Mg(NO;,) Mg(NO .6H O; 12.5% 3 months '20 6 months 35 2:10 ZnCl 0.5 Zn(NOZn(NO,,) .6H O; 25% 6 months l0 Na CO NaCl; 1.0 Mg(NO Mg(NO .6H O; 25% 6months 35 Na CO NaCl; l.0 Mn(NO Mn( 0.1)2; 25% 6 months 0 nitrates andmtrites are stored at 50C for the time indl- EXAMPLE 5 Gated andevaluated by gas hqu'd Chromatography 40 This example shows the effectof various metal salts (glc) to determine the amount of decomposition ofthe isothiazolone. Table III summarizes the results of these tests.

TABLE III DECOMPOSITION OF METAL SALT COMPLEX IN AQUEOUS SOLUTION MetalNitrate Nitrate Time Decomposition none days 100 Ca(NO .4H O 128.7 3months 10 4.5 months 6 months 9 months 55 Ca(NO;,) .4H O 125.0 2 months0 3 months 10 6 months 10 Ca(NO .4H O l4.3 1 month 10 3 months 45 4.5months 95 Cu(NO .3H O 135.8 3 months 5 4.5 months 10 6 months 10 9months 20 Cu(NO:.)-,.3H O 25.0 3 months 0 6 months (u(N();,) .Jll O I24)3 months 5 4.5 months 6 months 30 9 months Mn(N(); 125.0 6 months l0Mg(N();,) .6H,O 25.0 6 months It) Zn(No,-,) .6H O 25.0 6 months 5 none14 days 100 Ca(NO .H O .25 I4 days 0 NaNO 1125 14 days 5 in stabilizingaqueous solutions of3-isothiazolones. The 3-isothiazolone used in makingthe aqueous solutions is a 3:1 weight ratio of5-chloro-2-methyl-3-isothiazolone and 2-methyl-3-isothiazolone. Aqueoussolutions containing 25 percent by weight of the 3-isothiazolone and 0.5or 1.0 mole-equivalent of a metal salt are prepared, stored for up to 84days at 50C, and rated as in Example 1. Table V summarizes the resultsof these tests.

TABLE V AQUEOUS SOLUTIONS OF S-CHLORO-Z-METI-IYL-3-ISOTHIAZOLONE/2-METHYL-3-ISOTHIAZOLONE (25% by weight, 50C)The above results show the effectiveness of metal nitrates instabilizing aqueous solutions of 3- isothiazolone.-s and the generalineffectiveness of other metal salts as stabilizers.

EXAMPLE 6 'lhis example shows quantitatively the extent to whichchemical decomposition of 3-isothiazolones in solution is inhibited bymetal nitrates.

Two aqueous solutions of the 3-isothiazoiones (25 percent by weight)used in Example 5 containing 0.5

and L mole-equivalent of copper nitrate are evaluatedby glc to determinethe amount of decomposition of the isothiazolone. Table VI summarizesthe results of these tests trates in stabilizing nonztqueous summarizesthe results of these tests.

TABLE VIII NON-AQUEOUS SOLUTIONS OF 5-CHLORO-2-MElHYLJ-ISOTHIAZOLONECALCIUM (II)CHLORIDE/Z-METHYL-B-ISOTHIAZOLONE CALCIUMtII) CHLORIDE (50C)Isothiazolone Wt. /2, Metal Nitrate; wt. 7: Solvent Time 7:Decomposition 25% none dipropylene glycol l month 100 25% Ca(NO .4H O;dipropylene glycol 2 months 5 2571 Ca(NO;,) .4H O; 20% dipropyleneglycol 3 months 9 months 35 257r Mg(NO;,) .6H O; 10% dipropylene glycol2 months 5 2572 Mg(NO, .6H O; dipropylene glycol 3 months 5 .9 months 205% none methyl cellosolve 3 months 90 571' Ca(NO .4H O; 5% methylcellosolve 3 months 10 10% none methyl cellosolve 3 months 95 10% Ca(NO.4H O; 10% methyl ccllosolve 3 months 0 TABLE VI EXAMPLE 8 AQUEOUSSOLUTIONS OF S-CHLORO-Z'METHYL- 3-ISOTHIAZOLONE/Z-METHYL-B-ISOTHIAZOLONEby weight. 50C) Metal Salt Mole-equiv. Time Decomposition none none 10days 70 CZI(NO:|)2 1.0 3 months 0 Cu(NO;,) 0.5 3 months 5 9 months 5Cu(NO 1.0 3 months 0 9 months 5 Similarly, aqueous/methyl cellosolvesolutions (20/80) of k2-n-octyl-3 isothiazolone (compound A) and4-bromo-5-chloro-2-methyl-3-isothiazolone (compound B) stabilized withvarious metal nitrates are evaluated by glc to determine the amount ofdecomposition of the isothiazolones. Table VII summarizes the results ofthese tests.

TABLE VII AQUEOUS/METHYL CELLOSOLVE SOLUTIONS OF 3-ISOTHIAZOLONES (1month. 50C) Metal Nitrate (om- Weight 7c 25% by wt. 70 Decompositionpound A 20 none 100 A 20 Ca(NO ),.4H O 5 A l5 Mg(NO .6H O 15 A 15 Zn(NO.6H O 10 B 23 none 100 B 23 Ca(NO3)2-4H O 25 EXAMPLE 7 This exampleshows the effect of various metal ni- TABLE IX NONAQUEOUS SOLUTIONS OF 5CHLORO-Z-METHYL-S-ISOTHIAZOLONE/ 2METHYL-3-ISOTHIAZOLONE (93:7) (25% byweight, 50C) Metal Nitrate Appearance (days) (I mole-equiv.) SolventFailed Passed none dipropylcne glycol 28* 23 Ca(NO dipropylene glycol 84Zn(NO dipropylene glycol 84 none methanol l0 Ca(NOal2 methanol 84Zn(NO.1)2 methanol 84 "Solution gelled and became cloudy; glc showeddecomposition.

The non-aqueous solutions of 3-isothiazolones used in Example 8containing 1.0 mole-equivalent metal nitrates are evaluated by glc todetermine the amount of decomposition of the isothiazolone. Table Xsummarizes the results of these tests.

9 TABLE it NON-AQUEOUS SOLUTIONS OF S-CHLORO-Z-METHYL-3-ISOTHIAZOLONE/lE-METHYL-3-lSOTHlAZOLONE (93:7) {25% by weight, 50C) Metal NitrateDecompll mole-equiv) Solvent Time osition none itlipropylene glycol .18days lOO Ca(NO;,) lLiipropylene glycol 3 months Zn(NO dipropylcne glycol.3 months 16 Ca(NO me an 13 months 3 Zn(NO methanol 3 months 35 whereinY is a hydrogen atom, an alkyl group of 1 to 18 carbon atoms. an alkenylor alkynyl group of 2 to l8 carbon atoms, a cycloalkyl group of 3 to 12carbon atoms having a 3 to 8 carbon atom ring, an aralkyl group of up to10 carbon atoms, or an aryl group of up to 10 carbon atoms;

R is a hydrogen atom, a halogen atom, or a (C -C alkyl group; and

R is a hydrogen atom, a halogen atom, or a C -C alkyl group or R and Rcan be taken together to complete a benzene ring; which comprisesincorporating in the solution a stabilizing amount of a metal saltselected from the group consisting of metal nitrates, metal nitrites andmixtures thereof, wherein the metal is selected from the groupconsisting of sodium, potassium, calcium, magnesium, copper, iron,nickel, zinc, barium, manganese, silver, and cobalt.

2. The method of claim 1 wherein the solution is an aqueous solution.

3. The method of claim 1 wherein the metal salt is added in an amount ofabout i to about 30% by weight of the solution.

4. The method of claim 3 wherein the metal salt is calcium nitrate.

5. The method of claim 3 wherein the metal salt is magnesium nitrate.

6. The method of claim 3 wherein the 3-isothiazolone is2-n-octyl-3-isothiazolone.

7. The method of claim 3 wherein the 3-isothiazolone is5-chloro-2-methyl-3-isothiazolone or a mixture of 5-chloro-2-methyl-3-isothiazolone and 2-methyl-3- isothiazolone.

8. The method of claim 1 wherein the solution is an

1. A METHOD OF STABILIZING AN AQUEOUS OR POLAR ORGANIC SOLVENT SOLUTIONCONTAINING A MICROBIOCIDAL 3-ISOTHIAZOLONE AGAINST CHEMICALDECOMPOSITION OF THE 3-ISOTHIAZOLONE WHEREIN THE 3-ISOTHIAZOLONE HAS THEFORMULA
 1. A method of stabilizing an aqueous or polar organic solventsolution containing a microbiocidal 3-isothiazolone against chemicaldecomposition of the 3-isothiazolone wherein the 3-isothiazolone has theformula
 2. The method of claim 1 wherein the solution is an aqueoussolution.
 3. The method of claim 1 wherein the metal salt is added in anamount of about 1 to about 30% by weight of the solution.
 4. The methodof claim 3 wherein the metal salt is calcium nitrate.
 5. The method ofclaim 3 wherein the metal salt is magnesium nitrate.
 6. The method ofclaim 3 wherein the 3-isothiazolone is 2-n-octyl-3-isothiazolone.
 7. Themethod of claim 3 wherein the 3-isothiazolone is5-chloro-2-methyl-3-isothiazolone or a mixture of5-chloro-2-methyl-3-isothiazolone and 2-methyl-3-isothiazolone.